The adipocyte P2 (aP2) gene contains a regulatory element, FSE2, that functions during adipocyte differentiation and binds a protein complex containing the product of the fos proto-oncogene (Fos). We show here that the quantitative and qualitative nature of the FSE2 binding complex closely reflects the status of Fos expression within a given cell type. There is a dramatic increase in the FSE2 binding complex when Fos levels are induced with serum, benzodiazepine, and nerve growth factor or are expressed from a v-fos gene. Immunoblotting analysis of DNA retardation gels indicates a comigration of FSE2 complex with the predominant Fos species. Using a combination of mutational analyses of FSE2 and competition for binding with related sequences, we show that the Fos complex recognizes DNA containing the sequence TGACTCA, previously identified as the consensus binding site for the transcription factors AP-1 in mammalian cells and GCN4 in yeast. The simultaneous presence in cell extracts of proteins related to both AP-1 and Fos with similar sequence recognition properties was demonstrated by photo-cross-linking to FSE2 DNA and immunoprecipitating with antibodies directed toward c-fos or v-jun. These results suggest a functional relationship between Fos and AP-1.